Nosocomial pneumonia remains a common problem and is the leading cause of death among patients with nosocomial infection. However, the initial empiric therapy of nosocomial pneumonia is directed at the leading organisms common to all patients, and for many patients monotherapy is adequate for at least 48 hours, at which time the microbiological results of appropriate diagnostic procedures should be known and the treatment can be focused. The currently available antimicrobial agents such as third- and fourth-generation cephalosporins, piperacillin plus tazobactam, carbapenems, and some fluoroquinolones are highly active and bactericidal. They should be used in consideration of current pharmacodynamic knowledge, which will lead to convincing clinical results. Combination of antibiotics is necessary only in specific situations or for the amelioration of special pathogens, such as Pseudomonas aeruginosa, Acinetobacter spp., and against mixed aerobic and anaerobic infections.